question

3 most common gynecologic malignancies

answer

1. adenomocarcinoma of the endometrium 2. Epithelial ovarian cancer 3. Squamous cell carcinoma of the cervix

question

Type I endometrial cancer

answer

-*Estrogen related* -younger perimenopausal patients -*heavier patients* -low grade

question

Type II endometrial cancer

answer

-*Unrelated to estrogen* -*older patients* -thinner patients -*aggressive* -Potential genetic basis: Lynch Syndrome (but can be associated with either type, more commonly II)

question

Most common sites for cancers of the female reproductive tract

answer

-Uterine corpus not including the cervix -ovaries -uterine cervix

question

Less common sites for cancers of the female reproductive tract

answer

-Fallopian tubes -vagina -Vulva/perineum -placenta

question

Most common type of cancer in the female reproductive tract

answer

Carcinomas

question

Most common site for sarcomas in the female reproductive tract

answer

Uterine corpus

question

Other types of cancers that occur in the female reproductive tract

answer

Melanomas and lymphomas

question

Ovarian cancer risk

answer

1 in 70

question

Uterine cancer risk

answer

1 in 40

question

Cervical cancer risk

answer

One in 140

question

Breast cancer risk

answer

One in 8

question

Risk factors for type I endometrial cancer

answer

-Obesity ? >50 lbs overweight = 10X relative risk -extended reproductive life -nulliparous -late menopause -hypertension -diabetes type I and type II -Exogenous estrogen (unopposed) *think more years of ? estrogen, and HTN and DM*

question

Percent of endometrial carcinomas that are type I

answer

80%

question

Atypical hyperplasia

answer

in-situ Phase that precedes type I endometrial carcinoma -characterized by increased* gland to stroma ratio* -histologically there are enlarged in round nuclei, loss of cell polarity, and prominent nucleoli

question

atypical hyperplasia rate of progression to carcinoma

answer

8 to 25% or higher

question

Endometrial endometriod carcinoma

answer

Characterized by confluent glands or solid sheets of tumors *type I*

question

Percent of type I endometrial carcinomas that have mutations in the *PTEN tumor suppressor gene*

answer

80%

question

Percent of endometrial hyperplasia is that have a *PTEN mutation*

answer

20%, which supports the theory that It is a precursor lesion

question

Risk factors for type II endometrial adenocarcinoma

answer

-lean women -African-American

question

Percent of endometrial carcinoma is better type II

answer

15%

question

Type II endometrial carcinoma histology

answer

*serous* -Cells with very high nuclear to cytoplasmic ratios -numerous, atypical mitoses

question

Percent of patients with type II serous endometrial carcinomas that have mutations in the p53 tumor suppressor gene

answer

>90%

question

Presentation of endometrial cancer

answer

-Most common presenting complaint is postmenopausal or abnormal perimenopausal bleeding

question

true or false: bleeding after menopause is NEVER normal

answer

True

question

Only life-threatening cause of postmenopausal bleeding

answer

Cancer

question

Percent of postmenopausal bleeding that is accounted for by cancer

answer

20%

question

Who Needs an Endometrial Biopsy?

answer

1. Abnormal bleeding -*Postmenopausal bleeding* - Perimenopausal intermenstrual bleeding - Bleeding with history of anovulation 2. Postmenopausal women with endometrial cells on Pap test 3. Thickened endometrial stripe via sonography - Especially an *endometrial thickness of >5 mm in a postmenopausal woman*

question

Staging Endometrial/Uterine and Ovarian Cancer

answer

-Staging is* surgical/pathologic* -performing a predefined operation and assigning stage based on pathological evaluation of tissues removed

question

Goals of endometrial cancer staging

answer

- define the extent of the disease - minimize both over and under use of adjuvant treatment - decrease both patient risks and costs associated with treatment - allow for optimal comparison of outcomes

question

Components of endometrial cancer staging

answer

-Abdominal exploration -peritoneal cytology -total abdominal hysterectomy -bilateral salpingo-oopherectomy -bilateral pelvic and aortic lymph node dissection

question

Stage I

answer

Confined to uterus: A) endometrium only or 1/2 myometrium

question

Stage II

answer

Cervix involvement A: glands only B: stromal invasion

question

Stage III

answer

Uterine serosal adnexal disease positive cytology vaginal mets pelvic or aortic node involvement

question

Stage IV

answer

Bladder or bowel invasion inguinal nodes involved other distant metastases *not curable*

question

Survival rates of surgical stage one disease

answer

-In the absence of pathologic porpoise factors, surgery can be therapeutic with survival rates = 90-98%

question

Pathologic risk factors for recurrence of disease

answer

-High histologic *grade* (2 or 3) -depth of *myometrial invasion* -tumor* size* (>2 cm) -presence of* lymph-vascular* space invasion -*aggressive histologic cell type* (serous or clear cell cancer) the presence of 2 or more of these risk factors increases the recurrence rate to as high as 30% and justifies the use of postoperative adjuvant therapy

question

Stages II-IV

answer

Requires adjuvant therapy -generally pelvic radiation therapy with vaginal cuff boost -chemo therapy for cases with adnexal, nodal, or distant metastases

question

Percent of all endometrial cancers that are stage I

answer

70%

question

Percent of all endometrial cancers that are staged II

answer

18%

question

Percent of all endometrial cancers that are stage III

answer

8%

question

Percent of all endometrial cancers that are staged IV

answer

4%

question

Overall survival rate of stage I endometrial cancer

answer

76%

question

Overall survival rate of stage II endometrial cancer

answer

60%

question

Overall survival rate of stage III endometrial cancer

answer

30%

question

Overall survival rate of stage for endometrial cancer

answer

10%

question

Recurrent disease

answer

-Generally considered incurable -exception is isolated vaginal cuff recurrence and a woman who has not received adjuvant radiation

question

management of recurrent disease

answer

platinum-based chemotherapy participation in clinical trials is encouraged

question

Endometrial Cancer: Adjuvant Postoperative Therapy

answer

Whole Pelvic Radiation and Vaginal Cuff Boost Most common indications - cervical spread (stage II) - nodal involvement (stage IIIC) Can reduce recurrence rate by up to 50% Estimated cost 5,040 cGy PRT: $20,000 Treatment duration: 25 to 30 days Chemotherapy

question

Ovarian Cancer

answer

- Second most common gynecologic malignancy in the US - Responsible for 25,000 cases annually - 14,500 deaths annually - *Most lethal gynecologic malignancy * - 70% of patients present with advanced disease - no effective screening

question

Most common source of malignant ovarian tumors

answer

Surface epithelium

question

Risk factors for ovarian cancer

answer

-Age/postmenopausal -family history/genetics -infertility/low parity or other factor resulting in uninterrupted ovulation -personal cancer history (most commonly breast cancer) *has to do with ovulation, increased # of ovulations, means more repair to the ovaries = ? risk*

question

Factors that reduce the risk for ovarian cancer

answer

-Oral contraceptive use -pregnancy -tubal ligation -breast-feeding

question

Most common presenting templates for ovarian cancer

answer

-Abdominal bloating -early satiety -small or large bowel obstruction -many women do seek medical attention earlier in the disease process but symptoms are overlooked as minor gastrointestinal or genitourinary conditions such as *irritable bowel or UTI*

question

Definitive diagnostic modality for ovarian cancer

answer

Surgical exploration/pathology

question

Most common histologic subtype of epithelial ovarian cancer

answer

Serous carcinoma

question

2 categories of serous carcinoma of the ovary

answer

-Low grade -high-grade

question

Mutations commonly seen with low-grade serous cancers of the ovary

answer

- KRAS - BRAF - PTEN - B-catenin

question

Type of serous ovarian cancer with better purposes

answer

Low grade

question

Mutations associated with high-grade serious cancers of the ovary

answer

p53

question

The vast majority of epithelial covariant cancers are of which grade?

answer

High grade serous

question

Reason why the serum tumor marker CA125 and pelvic ultrasound are not reliable screening tests for ovarian cancer?

answer

-Lack the sensitivity (too many false negatives) -lack the specificity (too many false positives)

question

Management of ovarian cancer

answer

-Involves both surgery and systemic adjuvant, platinum and taxane paste chemotherapy

question

2 major surgical concepts of important in ovarian cancer

answer

-Complete surgical staging of disease that clinically appears to be confined to the ovaries -cytoreductive surgery or debulking

question

Complete staging of ovarian cancer

answer

-Peritoneal cytology -TAH/BSO -omentectomy -peritoneal biopsies from pelvis, mid abdomen, and diaphragmatic surfaces -pelvic and aortic node dissections

question

Ovarian Cancer: CA125 Testing

answer

- Elevated in > 80% of advanced EOCs and functions well as a tumor marker in majority of these cases - Elevated in 25-50% of Stage I cancers ? POOR SENSITIVITY - Elevated by many non-malignant conditions especially in premenopausal women ? POOR SPECIFICITY - NOT a screening test for the general population

question

Stage I ovarian cancer

answer

*Confined to the ovaries* A ? one ovary B ? both ovaries C ? one or both with surface disease or positive cytology

question

Stage II ovarian cancer

answer

*Confined to the Pelvic Organs*

question

Stage III ovarian cancer

answer

*Spread to the Upper Abdomen* (lymph nodes) A ? microscopic disease only B ? Largest lesion 2cm ( most common overall stage)

question

Stage IV ovarian cancer

answer

*Malignant pleural effusion or liver mets*

question

Percent of ovarian cancers that appear confined to the ovary (stage I) in which there is microscopic spread upstaging to stage IIIC

answer

30%

question

Key to a good outcome of ovarian cancers that have spread beyond the ovaries

answer

Tumor mass reduction and debulking -the more tumor removed, the better chance for survival

question

Optimal surgical debulking

answer

*leaving no tumor nodule >0.5 cm *

question

Post operative edge event chemotherapy for ovarian cancer

answer

Required in all cases other than stage IA grade 1 lesions

question

most common drug combinations used in Ovarian cancer chemotherapy

answer

-IV carboplatin and Taxol -intraperitoneal cisplatin and Taxol

question

Percent of women that will have good response to chemotherapy and will be in remission after 6 to 8 cycles of therapy

answer

70-80%

question

Percent of women who reach remission that will have a recurrence within the 1st 3 years after completing treatment

answer

>50%

question

Therapy for ovarian cancer recurrence

answer

-Reoperation for debulking -pretreatment with chemotherapy

question

Cure rate of recurrent ovarian cancer

answer

0%; considered incurable

question

percent of ovarian cancers that are diagnosed as stage I

answer

24%

question

Percent of ovarian cancers that are diagnosed in stage II

answer

6%

question

Percent of ovarian cancers that are diagnosed in stage III

answer

55%

question

Percent of ovarian cancers that are diagnosed as stage IV

answer

15%

question

Percent survival of stage I ovarian cancer

answer

95%

question

Percent survival of stage II ovarian cancer

answer

65%

question

Percent survival of stage III ovarian cancer

answer

15-30%

question

Percent survival of stage IV ovarian cancer

answer

0-20%

question

Overall survival rates of ovarian cancer

answer

50%

question

Surgical Rx for Early Stage ovarian cancer Disease

answer

*TAH BSO + staging * Infracolic omentectomy Peritoneal samples pelvis, gutters, diaphragm Pelvic and aortic lymph node dissection -In younger women, reproductive conservation may be appropriate -Approximately 30% will have histologic evidence of metastatic disease when clinically disease appears confined to the ovary

question

Surgical Treatment for Advanced ovarian cancer Disease

answer

Significant survival advantage for women optimally cytoreduced Procedures may include: En bloc resection of uterus, ovaries and pelvic tumor Omentectomy Bowel resection Removal of diaphragmatic and peritoneal implants Splenectomy, appendectomy

question

Ovarian Cancer Chemotherapy

answer

- All patients should receive a taxane and a platinum - 73% response rate, however more than half of these women will experience recurrence of the disease - Median survival: 38 months for Stage III/IV - Many new agents being tested - Encourage clinical trial participation

question

Ovarian Cancer Follow-up

answer

-Recto-Vaginal pelvic exam and CA125 q 3-4 mo x 2 years, q 6 mo for years 3-5 - CT scan for symptoms - General health maintenance (mammography, Pap smear, bone density, colon-rectal screening, cholesterol, etc.) - Discuss HRT, diet, exercise

question

Cervical Cancer Incidence

answer

American Cancer Society Estimates 12-13,000 cases of invasive cervical cancer/year 4600 of these women die International estimates Approximately 500,000 deaths/year! Number 1 or 2 cancer killer of women worldwide

question

Cervical Cancer Risk Factors

answer

-Early age of intercourse -Number of sexual partners -Smoking -Lower socioeconomic status -High-risk male partner -Other sexually transmitted diseases -Up to 50% of the U.S. population is infected with HPV

question

Percent of cervical cancers worldwide contain Human Papilloma Virus DNA

answer

*99.7%*

question

Cervical cancer screening

answer

Pap test

question

Percent of cervical cancers accounted for by type 16 HPV

answer

60%

question

Percent of cervical cancers accounted for by type 18 HPV

answer

10%

question

HPV infections locations

answer

-Basal cells of the squamous epithelium, usually at the squamocolumnar junction of the cervix

question

koilocytosis

answer

Squamous cell with a dark, irregular nucleus and a sharply defined perinuclear halo which is characteristic of HPV infection

question

Low-grade or mild dysplasia

answer

Cervical Intraepithelial Neoplasia grade 1

question

high grade or severe dysplasia

answer

Cervical Intraepithelial Neoplasia grade 3"

question

Why does the Pap test work?

answer

- cervix can be sampled relatively non-invasively - natural history of cervical cancer is slowly progressive - dysplastic (pre-invasive) changes can be recognized microscopically - dysplastic (pre-invasive) changes can be treated and prevented from progressing to invasive cancer - test is relatively inexpensive - HPV testing is integrated into screening in patients over 29 years of age (extends interval)

question

Cervical Cancer Prevention

answer

*HPV vaccination* available in US since 2006 recommended to males and females age 9-26 years 3 dose schedule

question

Where HPV viral particles are found in epithelial cells

answer

-Halo area

question

Treatment of cervical squamous cell dysplasia

answer

conization Cryotherapy

question

Oncogenesis from HPV

answer

Occurs when the virus becomes integrated into the host DNA and viral E6 and E7 proteins bind to retinoblastoma tumor suppressor genes and to the p53 tumor suppressor gene

question

mild cervical squamous cell dysplasia definition

answer

Abnormal cells confined to the lower 1/3 of the epithelium

question

Moderate cervical squamous cell dysplasia definition

answer

Abnormal cells extend into the middle 1/3

question

Severe dysplasia definition

answer

Abnormal cells are present in the superficial 1/3 of the epithelium

question

Signs and Symptoms of Invasive Cervical cancer

answer

May be silent until advanced disease develops *Post-coital bleeding* *Foul vaginal discharge* *Abnormal bleeding* Pelvic pain Unilateral leg swelling or pain Pelvic mass Gross cervical lesion

question

Most common presenting complaints for women with invasive squamous cell carcinoma

answer

Painless postcoital bleeding

question

Clinical staging of cervical squamous cell carcinoma

answer

-General physical exam -rectovaginal bimanual pelvic exam -plain film chest x-ray -cytoscopy and/or proctoscopy -intravenous pyelogeram

question

Type of staging used for cervical cancer

answer

-Unlike the other 2, it is *staged by clinical criteria* rather than surgical/pathologic staging

question

Type of staging used for ovarian cancer

answer

Surgical/pathologic staging

question

Type of staging used for uterine cancer

answer

Surgical/pathologic staging

question

Rationale for clinical staging of cervical cancer

answer

-The majority of squamous cell carcinoma affects women in the underdeveloped world where access to diagnostic modalities are limited or unavailable -continued clinical staging allows for comparison across every different geographic and socioeconomic population

question

Stage I cervical cancer

answer

*Confined to cervix* - A < 5mm invasion or 7mm lateral spread - B any lesion larger than IA microscopic or any visible lesion

question

Stage II cervical cancer

answer

*Vaginal and/or Parametria involved* A ? Upper 2/3 vagina B ? Parametria but not to the pelvic sidewall

question

Stage III cervical cancer

answer

*Extensive Vaginal or Parametria* A ? Lower 1/3 vagina B ? Parametria to the sidewall or any lesion causing hydronephrosis

question

Stage IV cervical cancer

answer

Distant Disease A ? Bladder or Rectal mucosa invasion B ? Distant mets

question

Treating Early Cervical Cancer

answer

1. Conization or simple hysterectomy - microinvasive cancer 2. Radical hysterectomy - removal of the uterus with its associated connective tissues, the upper vagina, and pelvic lymph nodes. Ovarian preservation is possible. 3. Chemoradiation therapy

question

Cervical Cancer Treating Advanced Cervical Cancer

answer

*Chemoradiation is the mainstay of treatment* - 4-5 weeks of external radiation - Two or more implants (brachytherapy) - Concurrent Cisplatin-based chemotherapy significantly improves the chances of survival - Radiation treats the primary tumor and adjacent tissues and lymph nodes - Chemotherapy acts as a radiation sensitizer and may also control distant disease

question

Cervical Cancer recurrence management

answer

Palliative chemotherapy Pelvic exenteration (if central recurrence) 50% cure rate

question

Five-year survival of stage I cervical cancer after treatment with radical hysterectomy

answer

85-98%

question

Five-year survival of stage I cervical cancer after treatment with chemo and radiation therapy

answer

85-95%

question

Five-year survival of stage II cervical cancer after treatment with chemo and radiation therapy

answer

70-80%

question

Five-year survival of stage III cervical cancer after treatment with chemo and radiation therapy

answer

50-65%

question

Five-year survival of stage IV cervical cancer after treatment with chemo and radiation therapy

answer

20-30% (IVA) <10% (IVB)

question

endometriod

answer

Type I endometrial carcinoma

question

serous

answer

Type II endometrial carcinoma

question

BRCA 1 or BRCA2 germline mutation

answer

35-65% lifetime risk of ovarian cancer

question

types of ovarian cancer

answer

>90% are surface epithelial cancers (serous)

question

postcoital bleeding

answer

rule out cervical cancer

question

postmenopausal bleeding

answer

rule out uterine (endometrial) cancer

Gynecologic Malignancies – Flashcards

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